Oral Manifestations Associated with COVID-19 Infection: A Cross-Sectional Study of Recovered Iraqi Patients

Aims The aim of this study was to determine prevalence of oral manifestations related to COVID-19 infection among a sample of recovered patients in the Basrah province of Iraq. Methodology. This cross-sectional study included a total of 574 individuals from Basrah city, Iraq (196 males and 378 females), who had been previously infected with COVID-19. A questionnaire was developed and used to record the demographic data, medical history, severity of respiratory infection followed by hospitalization along with oral signs and symptoms that occurred during the COVID-19 infection and their persistence after recovery. Results Oral manifestations were reported in 88.3% of the studied sample. The most common oral manifestation was ageusia (66.8%), followed by dry mouth (59%), gustatory changes (46%), dysphagia (40.5%), burning sensation (20.8%), oral ulceration (14.5%), and gingival bleeding (3.3%). The findings suggested that ageusia was the only symptom that persisted following recovery from the COVID-19 infection. The results showed a significant statistical correlation between the incidence of oral manifestations and the severity of COVID-19 infection followed by hospitalization. A significant correlation was also found between the age groups and COVID-19 oral manifestations, whereas no significant statistical relationship was observed between gender, smoking, and systemic diseases. Conclusions COVID-19 infection has considerable impacts on the oral cavity and salivary glands and after recovery from the infection, some patients continue to complain of ageusia for several months. There is a positive correlation between the incidence of oral signs and symptoms associated with COVID-19 infection and the severity of the infection.


Introduction
It has been more than two years since the recording of the frst case of the novel coronavirus disease  in Wuhan City, China, and the declaration by the World Health Organization (WHO) of pandemic disease [1] but we could not identify the Wuhan City case as the truly frst case all over the world. Since that time, approximately 643 million infection cases worldwide with more than 6 million deaths had been reported [2]. Fever, sore throat, severe headache, loss of smell and taste, shortness of breathing, dry cough, and tiredness are considered as the most common symptoms associated with the COVID-19 infection [3]. Tis viral disease is transmitted from human to human through respiratory droplets [4]. Previous studies have established that the SARS-CoV-2 virus invades human cells through an interaction with the host angiotensin-converting enzyme 2 receptors (ACE2) [5]. Tese receptors are expressed by a variety of human tissues such as lung, gastrointestinal tract, liver, kidney, skin, and the oral cavity [1,3]. Furthermore, the oral cavity has a crucial role in the dissemination of SARS-CoV-2 virus since it serves as a gateway to the internal environment of the human body. It has been suggested that oral manifestations associated with COVID-19 may be either related to the direct efect of the SARS-CoV-2 on the tissues of the oral cavity or an indirect efect due to an impairment of the immune system by the virus [6,7]. Oral manifestations related to COVID-19 infection have important negative impacts on nutrition, quality of life, and the psychological status of patients. In addition, they have an important role in the clinical diagnosis of disease [8].
Terefore, the aim of this cross-sectional study is to examine the types and prevalence of oral manifestations associated with COVID-19 and evaluates their persistence. In addition, any correlation between the incidence of these oral manifestations and several factors such as: gender, age, systemic disease, smoking, and severity of the infection have been investigated.

Methodology
2.1. Survey Procedure. Tis cross-sectional study was conducted on patients attending dental clinics of the College of Dentistry, University of Basrah, between October 2021 and April 2022. All the participants had been previously infected with COVID-19 and their infection was confrmed by a positive reverse transcription-polymerase chain reaction (RT-PCR) test.
Ethical approval was obtained by the Research Ethics Committee, College of Dentistry, Basrah University (BDC/ 07/09/2021), and the study was performed in accordance with Helsinki Declaration. All the participants were volunteers and had completed and signed a consent form.
Te study sample consisted of a total 574 patients from Basrah province (196 males and 378 females), with an age range between 18 and 78 years.
A questionnaire was flled out to collect information from each patient. Te patients were asked about their sex, age, occupation, address, smoking habits, the presence of any systemic diseases such as cardiovascular, respiratory, diabetes, cancer, kidney, and autoimmune disease and whether the respiratory infection was severe and required hospitalization. Details of any oral manifestations that occurred during the COVID-19 infection were recorded along with whether these persisted following the recovery.

Statistical
Analysis. Data were statistically analyzed using Microsoft Excel software. Te frequency and percentage were used to calculate the numerical data, whereas the Chi-square test was used to test signifcant statistical correlations. A p value of <0.05 was considered signifcant.

Results
Te results showed that 507 patients (88.3% of the total number of COVID-19 patients studies), had at least one manifestation related to the oral cavity and salivary glands. Whereas only 67 (11.7%) did not report any sign or symptom associated with oral cavity.
Te fndings showed that ageusia was the only symptom that persisted following recovery in 31% of the total patients who complained from ageusia for approximately one month, 4.6% for 3 months and 2.6% after 6 months ( Figure 2).
Regarding the gender of the patients, 172 (87.7%) males and 335 (88.6%) females had at least one oral sign and symptom associated with the COVID-19 infection. Tere was no statistically signifcant diference in the prevalence between the males and females (p � 0.7) as shown in Table 1.
With regards to the presence of systemic diseases, the results showed that 128 patients in the study sample had systemic diseases and 112 (87.5%) of them complained of at least one oral manifestation during their COVID-19 infection. On the other hand, 446 participants had no systemic diseases, and 395 (88.6%) of them showed oral signs or symptoms during the period of infection. No statistically signifcant diference was detected between the patients with systemic diseases and healthy patients (p � 0.7, Table 3).
Among 67 smokers in the study sample, 61 (91.1%) of them had at least one oral sign and symptom. Whereas the number of nonsmoker patients who were afected by oral manifestations was 446 forming 87.9% of the total number of nonsmoker patients. Tere was no statistically signifcant diference recorded between smoking patients and nonsmokers (p � 0.4, Table 4).
Finally, the fndings showed that 69 patients in the study sample was hospitalized during their COVID-19 infection due to the severe respiratory infection with 67 (97.1%) of them complaining of oral manifestations. 505 patients did not require admission to hospital and 440 (87.1%) of them had oral manifestations, a signifcant statistical diference between both groups (p � 0.01, Table 5).

Discussion
COVID-19 infection has efects on multiple organs and sites including oral cavity [1]. Although many studies have been published to investigate its general impacts, oral manifestations are still underestimated and unclarifed [9]. Terefore, the rationale of the current study was to investigate the most common oral manifestations that are accompanied by the disease, their prevalence as well as the presence of any correlations with demographic factors and the severity of disease in an Iraqi cohort.
Te results of the study showed that 66.8% of the examined patients had ageusia (complete loss of taste sensation) which is higher than that found by Ganesan et al.      [11]. Two hypotheses could explain the high incidence of ageusia and gustatory changes during COVID-19. First, high expression of ACE2 receptors in epithelial cells in taste buds of the tongue that binds SARS-CoV-2 virus results in inactivation of these receptors and as a consequence, the taste perception is alter [12][13][14]. Te second hypothesis suggests that taste loss might be attributed to side efects of medications used in the treatment of COVID-19 infection [15,16]. However, the later hypothesis is considered questionable and remains unsupported due to the occurrence of ageusia and gustatory changes in drug-free COVID-19 patients with mild and moderate infection [12]. Dry mouth (xerostomia) is the second most common oral fnding found in 59% of the total study sample which is comparable to that found by Ameen et al. (56%) but higher than that revealed by El Kady et al. (39.7%) [11] and Ganesan et al. (28%) [8]. Recent literature attributed the incidence of xerostomia during COVID-19 infection to prolong antibiotic treatment and poor hydration as well as the presence of Candida infection [8].
Te results of the current study showed dysphagia in 40.5% of the participants which is higher than that reported by El Kady [17].
In this study, the prevalence of burning sensation is 22.8% which is similar to that found by El Kady et al. (22.4%) [11]. Several studies suggested that burning sensation is a nonspecifc symptom that might occur during COVID-19 infection as a consequence of other conditions such as dry mouth, candidal infection, oral ulceration, and any secondary infection [1,18].
Our fndings showed that 14.5% of the studied sample complained of oral ulceration following COVID-19 infection which is comparable to that found by El Kady et al. (17.2%) [11] and higher than that found by Natto et al. (6.4%) [10]. Previous studies have considered oral ulceration to be a nonspecifc symptom and indirectly related to COVID-19. Tis could be due to several reasons such as blister as a result of high fever, aphthous ulcers triggered by stress, and recurrent herpes type 1 infection due to a compromised immune system during COVID-19 infection [19][20][21][22].
Te last oral manifestation investigated in this study was gingival bleeding which is found in 3.3% of the study sample, which is less than that reported by El Kady et al. (7%) [11]. Gingival bleeding could be explained by the fact that COVID-19, like other debilitating diseases leads to reduced measures of maintaining oral hygiene. Tis leads to the   International Journal of Dentistry accumulation of dental bioflm which is associated with an increased infammatory reaction and accompanied by clinical signs of gingivitis [23].
To the authors' best knowledge, no previous study has examined the persistence of oral signs and symptoms following recovery from the infection. Our results demonstrated that only ageusia continued in some patients for up to 6 months following the recovery. Tere is no specifc explanation for this as the exact pathogenesis of loss of smell and taste in COVID-19 is unknown [24]. Furthermore, many studies established that loss of taste accompanied olfactory dysfunction and most individuals considered both symptoms as a single entity rather than two [25].
In this study, the relationships between the incidence of oral manifestations with gender, age, smoking, systemic diseases, and the severity of infection were evaluated. Te results showed a signifcant statistical correlation between oral manifestations and age of patients as well as the severity of infection. Tese fndings are in consistent with the study by Ganesan et al. [8] who found no correlation between oral manifestations and gender and smoking, whereas a signifcant correlation was found with severity of the infection. In addition, the fndings are in accordance with that reported by El Kady et al. [11] who showed that there is no correlation between genders with oral manifestations.
It is obvious in the current study that the high frequency of the oral manifestations reported by hospitalized patients. Tis could be attributed to the fact that hospitalized patients had severe acute respiratory infection, and most of them were intubated and are likely to have an impaired immune response. Furthermore, those patients were debilitated and had a long hospital course. All these factors lead to compromised oral hygiene and a subsequent increased incidence of oral signs and symptoms [8].

Conclusions
It is evident that COVID-19 infection has signifcant efects on the oral cavity and salivary glands. Tese efects increased with severity of the infection and patient hospitalization. In addition, some patients continue to complain of loss of taste for several months after recovery from the infection. Terefore, it is recommended that the dentists should have the adequate knowledge of the patterns of presentation and management of common oral manifestations associated with COVID-19. Furthermore, it is also suggested that dentists should be part of the COVID-19 therapy team so as to improve the process of recovery and the quality of life for the afected patients.

Data Availability
Te data that support the fndings of this study are available from the corresponding author upon reasonable request.

Conflicts of Interest
Te authors declare that they have no conficts of interest.

Authors' Contributions
Mohanad JN Al-Magsoosi conceptualized the study, performed investigation, performed methodology, performed project administration, performed supervision, and wrote and edited the original draft. Oras KB Al-Asadi conceptualized the study, performed methodology, performed data curation, and wrote the original draft. Nibrass T Al-Quraine performed data curation and data analysis. Suha M Sami conceptualized the study and performed formal analysis. Julfkar Haider performed supervision; performed formal analysis; and wrote, reviewed, and edited the manuscript.